Limitation of tuning the antibody-antigen reaction by changing the value of pH and its consequence for hyperthermia

Abstract

Distribution of the isoelectric point (pI) was calculated for the hypervariable regions of Fab fragments of the antibody molecules, which structure is annotated in the structural antibody database SabDab. The distribution is consistent with the universal for all organisms dividing the proteome into two sets of acidic and basic proteins. It shows the additional fine structure in a form of the narrow-sized peaks of pI values. This is an explanation why a small change of the environmental pH can have a strong effect on the antibody-antigen affinity. To show this, a typical enzyme-linked immunospecific assay experiment for testing the reaction of goat anti-human IgA antibodies with human IgA immunoglobulins of saliva as antigens was modified in such a way that Fe3O4magnetic nanoparticles were added to PBS buffer. The magnetic nanoparticles were remotely heated by the radio frequency magnetic field providing the local change of temperature and pH. It was observed that short times of the heating were significantly increasing the antibody-antigen binding strength while it was not the case for a longer time. The finding discussed in the study can be useful for biopharmaceuticals using antibodies, the immunoassay techniques as well as for control over the use of hyperthermia.

The Concept of Using 2D Self-Assembly of Magnetic Nanoparticles for Bioassays

“…The placement of various functional amino and carboxyl groups on the surface of nanoparticles allows us to use them in a new type of immunoassay becoming competitive with conventional ELISA methods. In an earlier publication [13] of two co-authors of this work, it was shown that the presence of magnetic nanoparticles of iron oxide significantly increases the capacity of antibodies to recognize antigens by means of the formation of paratope-epitope-binding complexes. It was explained that the mechanism causing such an effect is a local change in pH in the surrounding nanoparticles.…”

“…Depending on the pH value of the solution, the presence of nanoparticles will lower the pH value or increase it in their immediate vicinity. Referring to paper [13] on catalyzing antibody-antigen reactions with magnetic nanoparticles, the catalytic capabilities of magnetic-nanoparticle chains can be extended by using alternating magnetic fields at radio frequencies. Once the energy of the alternating magnetic field absorbed by magnetic nanoparticles is released to the surrounding nanoparticles in the form of heat it can affect the pH level.…”

Enhancing silica surface deprotonation by using magnetic nanoparticles as heating agents

“…The analogous concept for local hyperthermia applied to cancerous tumor treatment is widely discussed in recent medical applications [2,3]. The particular example of the localized heating up by magnetic nanoparticles in the external radio-frequency magnetic field, as shown in the other work by some of the authors [39], might be the use of hyperthermia effect of magnetic nanoparticles Fe 3 O 4 to tune the antibody-antigen binding strength. Another example is the pH control of the oriented aggregation which becomes a new challenge for crystallography [40].…”

Methods in Raman spectroscopy for saliva studies – a review

“…[189,190] 2.5. General studies Mleczko et al [191] study the interaction of antibodies and antigens in saliva and the effect of magnetic hyperthermia, mediated by hematite (Fe 3 O 4 ) NPs acting to change local temperature and pH. Karlinsey et al [192] has studied the nucleation phase of hydroxyapatite on metal oxide with Raman spectroscopy in saliva, which may be of broad interest in biocompatibility studies with possible dental applications.…”